CMOS FET and AlGaN MODFET Receptor Scaffold for Molecular Recognition and Direct Detection

This project is designed to test a novel receptor scaffold/sensor combination for the selective and direct measurement of antigens and to compare direct electric detection of antigens against the corresponding antibody based ELISA method. The scaffold concept combines a robust nucleic acid receptor (aptamer) coupled to a low cost CMOS FET and AlGaN MODFET transducer. Aptamers are short nucleic acid polymer sequences (oligonucleotides) of between 20 and 80 nucleic acid residues. Aptamers can be isolated and tested for binding affinity with a variety of target molecules (e.g. pathogenic bacteria). Unlike antibodies, those aptamers with demonstrated affinity can then synthesized using high volume commercial methods unlike antibodies. They are also typically stable to heat and surface denaturation unlike antibodies, and can be synthesized with modified nucleotides so as to avoid degradation in most harsh biological or non-biological environments. Multiple candidate aptamers specific for a biological agent provides potential for validation and greater confidence in the detection process, and the CMOS FET transducer matches well the potential of aptamers to be able to quickly adapt to new biological and chemical threats. The FET for sensing applications was first reported thirty years ago. FETs can be manufactured in large quantities with consistent electrical properties using an industry standard process. In principal, the FET detects the charge redistribution as a result of aptamer binding the target molecule. The aptamers are linked closely to the sensor by a robust commercial process. Silane chemistry is used to modify the oxide surfaces of the FET channel region and the subsequent covalent bond to the protein avidin to produce a common surface for attaching a variety of different aptamers. Aptamer candidates are modified by the addition of biotin and attached to the avidin-modified surface. The resulting receptor modified surface has a potentially longer shelf life and active life in the field than do sensors where the receptor is physically adsorbed on a surface or embedded in a polymer matrix. It is unlikely that direct detection using aptamers will compete with the sensitivity of laboratory methods (ELISAs) using antibodies, but the aptamer sensor combination should be a more robust detection method requiring less maintenance than the antibody version of the same sensor and more flexible in adapting new threats.